As the most abundant protein in mammals, collagens play a crucial role in tissue development and regeneration, and their structural or metabolic abnormalities are associated with debilitating genetic diseases and various pathologic conditions. Although collagen remodeling occurs during development and normal tissue maintenance, particularly for renewing tissues (e.g. bones), excess remodeling activity is commonly seen in tumors, arthritis, and many other chronic wounds. During collagen remodeling, large portions of collagens are degraded and denatured by proteolytic enzymes which can be explored for diagnostic and therapeutic purpose. Since unstructured proteins are not ideal targets for rational drug design, library approaches have been employed to develop monoclonal antibody and peptide probes that specifically bind to cryptic sites in collagen strands that become exposed when denatured. However, these probes suffer from poor pharmacokinetics, and/or low specificity and binding affinity.
Fibrous collagens are major structural components of extracellular matrix in mammals; collagen overproduction is associated with many human diseases including cancers and fibrosis. Collagen is typically identified in biomedical research by western blot and immunohistochemistry; however anti-collagen antibodies employed in these analyses are difficult to prepare and their affinities to collagen can diminish if collagen becomes denatured during analyses.
Thus, there exists a need for new probes and techniques for detection of collagens both in vitro, using direct detection methods for gels and histology, as well as in vivo detection for collagens undergoing remodeling and therapeutics based on the same.